This proposal is to develop a HIV-1 specific nonnucleoside RT inhibitor. This compound has been shown to have EC50 values ranging from 0.4-1.7 microM against both laboratory and clinical HIV- isolates in the in vitro XTT assay. It is also active against HIV isolates with a mutation of Y181C, against 3TC-resistant isolates with an RT mutation of M184I, and against HEPT-resistant isolates with a mutation of P236L. Furthermore, the compound exhibits potent activity against human cytomegalovirus with an EC50 value comparable to that of ganciclovir. Further pharmacological and toxicological evaluations of the drug will be the focus of this phase I SBIR program, which include synthesis of one kilogram of (+)-12- oxocalanolide A, improving the synthetic processes of (+)-12- oxocalanolide A, and performing the acute single-dose toxicity studies. The toxicity study will examine oral and intravenous administration of the inhibitor in two mammalian species, and begin preliminary pharmacokinetic experiments. The ultimate goal for this SBIR program will be to file an IND application with the FDA at the end of the Phase II SBIR and to initiate a Phase I/II clinical trial.